Length requirements for membrane fusion of influenza hemagglutinin peptide linkers to transmembrane or fusion peptide domains

ZN Li, BJ Lee, WA Langley, KC Bradley, Rupert James Martin Russell, DA Steinhauer

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

During membrane fusion, the influenza A virus hemagglutinin (HA) adopts an extended helical structure that contains the viral transmembrane and fusion peptide domains at the same end of the molecule. The peptide segments that link the end of this rod-like structure to the membrane-associating domains are approximately 10 amino acids in each case, and their structure at the pH of fusion is currently unknown. Here, we examine mutant HAs and influenza viruses containing such HAs to determine whether these peptide linkers are subject to specific length requirements for the proper folding of native HA and for membrane fusion function. Using pairwise deletions and insertions, we show that the region flanking the fusion peptide appears to be important for the folding of the native HA structure but that mutant proteins with small insertions can be expressed on the cell surface and are functional for membrane fusion. HA mutants with deletions of up to 10 residues and insertions of as many as 12 amino acids were generated for the peptide linker to the viral transmembrane domain, and all folded properly and were expressed on the cell surface. For these mutants, it was possible to designate length restrictions for efficient membrane fusion, as functional activity was observed only for mutants containing linkers with insertions or deletions of eight residues or less. The linker peptide mutants are discussed with respect to requirements for the folding of native HAs and length restrictions for membrane fusion activity.

Original languageEnglish
Pages (from-to)6337-6348
Number of pages12
JournalJournal of Virology
Volume82
DOIs
Publication statusPublished - Jul 2008

Keywords

  • PH-INDUCED CONFORMATION
  • POTENT INHIBITORS
  • NEUTRALIZING ANTIBODY
  • ENVELOPE GLYCOPROTEIN
  • BINDING-PROPERTIES
  • HA(2) SUBUNIT
  • HIV-1 GP41
  • F-PROTEIN
  • A-VIRUSES
  • ECTODOMAIN

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